File Name: cytokines and hematopoietin receptors 2019 .zip
Interleukins ILs are a group of cytokines secreted proteins and signal molecules that were first seen to be expressed by white blood cells leukocytes. ILs can be divided into four major groups based on distinguishing structural features. The human genome encodes more than 50 interleukins and related proteins.
- The IL-12 Cytokine and Receptor Family in Graft-vs.-Host Disease
- T 0898/05 (Hematopoietic receptor/ZYMOGENETICS) of 7.7.2006
Principles of Cancer Biotherapy pp Cite as. Cytokines are regulatory proteins, produced and secreted by various cells, which control immune response, hematopoiesis, inflammation, wound repair and tissue morphogesis. Cytokines may be secreted or membrane bound.
Boards of Appeal Contact us using an online form. All contact information. Check the calendar of oral proceedings. For the purposes of Article 57 EPC, a claimed invention must have such a sound and concrete technical basis that the skilled person can recognise that its contribution to the art could lead to practical exploitation in industry, i.
It is necessary to disclose in definite technical terms the purpose of the invention and how it can be used in industrial practice to solve a given technical problem, this being the actual concrete benefit or advantage of exploiting the invention. The fact that a function is based on computer-assisted methods, rather than on the basis of traditional wet-lab techniques, does not mean that it has to be automatically disregarded or excluded from a careful and critical examination.
Their probative value has to be examined on a case-by-case basis regarding the nature of the invention and the prior art relating thereto cf. The function of a protein and thus of the nucleic acid encoding it can be seen at different levels, which include its molecular function, its cellular function and its biological function in a broad sense.
The elucidation of one of these particular levels of function might result, under certain conditions, in a straightforward industrial application, even though the other levels of activity remain completely unknown or only partially characterized. For the purpose of Article 57 EPC and Rules 23e 3 and 27 1 f EPC, none of these levels is more fundamental than the other ones insofar as at least from one of these levels a practical application a profitable use in a wider sense is derivable in a straightforward manner cf.
The applicant appellant lodged an appeal against the decision of the examining division dated 23 February whereby the European patent application No.
The decision under appeal was based on a main request and an auxiliary request filed with the applicant's letter of 16 February On 28 June , the appellant filed a statement of grounds of appeal wherein the requests before the examining division were maintained and re-filed.
The examining division did not rectify its decision and remitted the appeal to the board of appeal under Article 2 EPC. With the statement of grounds of appeal, the appellant also requested oral proceedings if the board was not prepared to grant a patent on the basis of the main request. After a telephone consultation with the board's rapporteur on 23 February , wherein the appellant's representative was informed of the preliminary positive opinion of the board on Article 57 EPC and of its intention to remit the case to the first instance, the appellant's representative, in its letter of 2 March , withdrew the request for oral proceedings if the board should find the application met the requirements of Article 57 EPC and Rule 23 EPC.
The main request comprised 15 claims, wherein independent claims 1, 9, 11, 12 and 15 read as follows:. An isolated polynucleotide, optionally DNA, encoding a ligand-binding receptor polypeptide, said polypeptide comprising a sequence of amino acids selected from the group consisting of:.
A chimeric polypeptide consisting of a first portion and a second portion joined by a peptide bond, said first portion consisting essentially of a ligand binding domain selected from the group consisting of:. A method for detecting a ligand within a test sample, comprising contacting a test sample with a polypeptide, optionally immobilized on a solid support, said polypeptide comprising a segment selected from the group consisting of:.
Claims 2 to 5 concerned particular embodiments of claim 1 and defined the presence of further elements in the ligand-binding receptor polypeptide a fibronectin type III domain, a transmembrane domain, an intracellular domain and an affinity tag, etc.
Claims 6 and 7 concerned expression vectors comprising several elements transcription promoter and terminator including a DNA segment encoding a secretory peptide and a ligand-binding receptor polypeptide of claims 1 to 5. Claim 8 referred to a cultured cell into which an expression vector according to any one of claims 6 to 7 had been introduced.
Claim 10 was directed to the polypeptide of claim 9 immobilized on a solid support. Claims 13 and 14 concerned particular embodiments of the method of claim The reasons given by the examining division in the decision under appeal may be summarised as follows:. The claimed protein was only characterized in structural terms and in terms of localization of expression, but not in functional terms. The structural relation between the Zcytor1 and the subfamily of cytokine receptors was established by computer-assisted alignment.
These studies did not allow any concrete conclusion to be drawn concerning the actual function of the protein but rather only speculations of a vague nature. However, this "function" the parentheses are used to indicate that the so -called function indicated is not considered to be an acceptable function in the context of the consideration of industrial applicability is so vaguely defined that no specific biological function which would implicate a therapeutic use or a diagnostic use has been defined" emphasis added.
It was further stated that the disclosed Zyctor1 was merely a research tool important for establishing a research program, i. It was only at this subsequent step not reached in the application that the actual function of Zcytor1 could be determined. In conclusion, no actual biological role or function was demonstrated and the members of the identified subfamily of cytokine receptors obviously all had different functions.
Hence, it was not at all clear which conditions could be diagnosed or treated using the protein Zcytor1 and what utility the protein or DNA could have. Since the function of Zcytor1 was not established in the application, the subject-matter of the claims did not fulfil the provisions of Article 57 EPC in combination with Rule 23 e 3 EPC. The existence of Rule 23 e 3 EPC required an examination as to whether or not the use requirement of Article 57 EPC was fulfilled, the answer in the present case being negative.
The appellant's arguments, insofar as they are relevant to the present decision, may be summarised as follows:.
Article 57 EPC provided two alternatives for an invention to be susceptible of industrial application, namely that it could be made or used in any kind of industry, including agriculture. Consequently, if the claimed invention could be made, it already met the requirements of the EPC as regards susceptibility of industrial application.
Even if the language of Article 57 EPC were interpreted as meaning that the "making" referred to had to be in industry, there was nothing to indicate that the word "industry" had a particular or narrow meaning. In the context of this broad nature of industry, the "could be made in industry" test was more than enough for any invention.
Rule 27 1 f EPC did not provide any further definition beyond that derivable from Article 57 EPC itself, it only imposed an additional practical requirement in case the way in which the invention was capable of exploitation in industry was not obvious from the description or the nature of the invention. So as not to conflict with the first option afforded by Article 57 EPC, the industrial application of a sequence or a partial sequence referred to in Rule 23e 3 EPC was satisfied merely by the explicit or implicit disclosure of the capability of making the relevant gene or sequence in any kind of industry.
This was in agreement with a narrow interpretation of this Rule, otherwise it would constitute a broadened exception to patentability contrary to the normal approach of the Boards of Appeal. Recitals 22 , 28 and 34 all emphasized and made clear that the legislative intention was not to change relevant basic law, inter alia, the provisions on susceptibility to industrial application.
Whereas in Recital 23 the patentability of a mere DNA was denied, immediately afterwards in Recital 24 it was specified that in connection with a gene sequence or partial gene sequence it was necessary to specify which protein or part of a protein was produced or what function it performed. This Recital thus asserted a choice of route whereby compliance with the industrial application criterion was achievable. If this Recital 24 was to be used, however, as requiring an indication of a use or of a function of a DNA sequence in a case where the requirements of Article 57 were satisfied merely by the capability of making the sequence in industry, then Recital 24 was in collision or conflict with the EPC since such a requirement was not derivable from Article 57 EPC itself.
However, it was not the Directive itself which was the governing law; it was the manifestation of the corresponding provisions in Rule 23 b - e of the Implementing Regulations to the EPC.
Thus, in case of a conflict, in accordance with Rule 23b 1 EPC, which stated that the Directive was only to be used as supplementary means of interpretation, the guidance of the Directive ceased and Rule 23 b - e EPC had to be interpreted in the normal way.
The use of a research tool was an appropriate basis for asserting susceptibility of industrial application in addition to and as an alternative to the capability of making a "gene sequence" invention in any kind of industry.
There was no requirement or legal provision in either the EPC or its Implementing Regulations that an invention relating to a gene sequence should have a therapeutic or diagnostic use as such. It was also a very long-established legal principle that exceptions to patentability were to be construed narrowly.
The imposition of a further or additional layer of restrictions in the form of a therapeutic or diagnostic use to the provisions of the Implementing Regulations, which were themselves narrower than the EPC, had no basis in law. If the board arrived at any different interpretation and conclusion with regard to Article 57 EPC and Rule 23 b - e EPC, important points of law were then involved and a referral to the Enlarged Board of Appeal was appropriate.
Several questions to the Enlarged Board of Appeal were specifically suggested for such a referral. The application explicitly described the Zcytor1 as a cytokine receptor with a role in the proliferation, differentiation and activation of immune cells; Zcytor1 was also implicated in the development and regulation of immune responses.
Specific applications based on the manipulation of the activity of the disclosed receptor were further disclosed. Whereas Zcytor1 agonists could be used in stimulating cell mediated immunity and lymphocyte proliferation, Zcytor1 antagonists could be used in the suppression of immune responses, such as in the treatment of autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, diabetes, etc. The statements made in the application had been confirmed to be correct. Applicant's unpublished data showed that soluble ILRA-Ig neutralised the biological activity of IL in vitro and that it diminished delayed-type hypersensitivity response in vivo.
Other researchers had published data showing that treatment with neutralising IL pspecific antibody products protected rodents from developing EAE and rheumatoid arthritis disease. Clearly, the application disclosed specific functions and uses of the Zcytor1 receptor that were factually accurate and confirmed by post-filed data.
There was no basis in the law for requiring a function of a sequence to be "specific" or for having any form of concern about the "vagueness" of a sequence's function. The examining division adopted the position that what was not "specific" was vague and, ipso facto, not enough for patentability.
This view ignored the law and went against basic common sense and fundamental fairness. In fact, functions upon which industrial activity could be supported were often general and not "specific" in the way the examining division meant. The appellant applicant requested that the decision under appeal be set aside and that a patent be granted on the basis of the main request or, alternatively, the auxiliary request as filed with the statement of grounds of appeal cf.
Section III supra. According to Article 52 1 EPC for a European patent to be granted an invention has to satisfy inter alia the requirement of being "susceptible of industrial application". According to Article 57 EPC, this requirement is fulfilled if the invention "can be made or used in any kind of industry, including agriculture". In this respect, Rule 27 1 f EPC prescribes that the description should "indicate explicitly, when it is not obvious from the description or nature of the invention, the way in which the invention is capable of exploitation in industry.
The case law indicates that the notion of "industry" has to be interpreted broadly so as to include all manufacturing, extracting and processing activities of enterprises that are carried out continuously, independently and for financial commercial gain cf. The latter decision gives some general guidance for assessing the compliance of biotechnological inventions concerned with substances found in nature e.
A distinction is made therein between i cases where, in addition to the structure of the substance in question, its function is also elucidated or is already known from the art, and ii cases where the substance is identified, and possibly also characterised, but either its function is not known or is complex and incompletely understood and there is no disease or condition attributable to an excess or deficiency of the said substance.
It is stated that in cases falling under i a practical industrial application of the substance in question can in general be easily seen and, if so, the requirements of Article 57 EPC are fulfilled, whilst in cases falling under ii if no practical application can be envisaged, industrial applicability cannot be acknowledged cf.
With reference to the second group of cases, the board indicated that "there must be a borderline between what can be accepted, and what can only be categorized as an interesting research result which per se does not yet allow a practical industrial application to be identified" and that "even though research results may be a scientific achievement of considerable merit, they are not necessarily an invention which can be applied industrially".
As seen above, the case law refers to the concepts of "financial commercial gain" cf. In the board's judgement, those two expressions both tend to convey the same idea: patents being an incentive to innovation and economic success, the criterion of "industrial applicability" requires that a patent application describes its subject invention in sufficiently meaningful technical terms that it can be expected that the exclusive rights resulting from the grant of a patent will lead to some financial or other commercial benefit.
The board considers that the need to show a "profitable use" is not to be understood in the narrow sense of an actual or potential economic profit i. Rather, it must be understood in the wider sense that the invention claimed must have such a sound and concrete technical basis that the skilled person can recognise that its contribution to the art could lead to practical exploitation in industry.
It would be at odds with the purpose of the patent system to grant exclusive rights to prevent the commercial activities of others on the basis of a purely theoretical or speculative patent application.
This would amount to granting a monopoly over an unexplored technical field. The board takes the view that, in the present context, the concept of "profit" should be seen in its wider sense of benefit instead of its narrower sense of financial reward.
Accordingly, the expression "profitable use" should be understood more in the sense of "immediate concrete benefit". This conveys, in the words "concrete benefit", the need to disclose in definite technical terms the purpose of the invention and how it can be used in industrial practice to solve a given technical problem, this being the actual benefit or advantage of exploiting the invention.
The essence of the requirement is that there must be at least a prospect of a real as opposed to a purely theoretical possibility of exploitation. Further, the use of the word "immediate" conveys the need for this to be derivable directly from the description, if it is not already obvious from the nature of the invention or from the background art. It should not be left to the skilled reader to find out how to exploit the invention by carrying out a research programme.
Not only is this the essence of the requirements of Rules 23e 3 and 27 1 f EPC, it also corresponds to the requirements of Articles 56 the need to provide a non-obvious solution to a technical problem , 57 the need to indicate how to exploit the invention , and 83 EPC the need to provide a sufficient disclosure of the claimed invention.
All those provisions reflect the basic principle of the patent system that exclusive rights can only be granted in exchange for a full disclosure of the invention. Accordingly, a product whose structure is given e. On the other hand, a product which is definitely described and plausibly shown to be usable, e. Thus, although no particular economic profit might be expected in the development of such products, nevertheless there is no doubt that it might be considered to display immediate concrete benefits.
It is considered useful at this point to see how the question of "industrial applicability" has been decided in some recent biotechnological cases. The application did not explicitly disclose the specific nature and the possible significance of these suggested roles for BDP1. The board found that the application stopped short of suggesting, let alone identifying for BDP1 an anti-cancer activity or a therapeutic use as a tumour-suppressor agent.
Thus, the board concluded that, although the application described a product a polypeptide , means and methods for making it, and its prospective use thereof for basic scientific activities, it identified no practical way of exploiting it in at least one field of industrial activity.
In the board's view, the only practicable use suggested was to use what was claimed to find out more about the natural functions of what was claimed itself.
The IL-12 Cytokine and Receptor Family in Graft-vs.-Host Disease
Allogeneic hematopoietic cell transplantation allo-HCT is performed with curative intent for high- risk blood cancers and bone marrow failure syndromes; yet the development of acute and chronic graft-vs. This family of cytokines is biologically distinct in that they are composed of functional heterodimers, which bind to cognate heterodimeric receptor chains expressed on T cells. More recently, IL was described as a potent anti-inflammatory agent produced by regulatory B and T cells. The role of the newest member, IL, has been implicated in proinflammatory B cell responses but has not been explored in the context of allo-HCT. This review is directed at discussing the current literature relevant to each ILfamily cytokine and cognate receptor engagement, as well as the consequential downstream signaling implications, during GVHD pathogenesis. Additionally, we will provide an overview of translational strategies targeting the IL family cytokines, their receptors, and subsequent signal transduction to control GVHD. Allogeneic hematopoietic cell transplantation allo-HCT is performed with curative intent for high-risk blood cancers and bone marrow failure syndromes.
Received: 31 March ; Accepted: 24 April ; Published: 29 April Abstract: Interleukin-9 (IL-9) is a pleiotropic cytokine and was primarily studied in the member of type I hematopoietin receptor superfamily, has high affinity (Kd of.
T 0898/05 (Hematopoietic receptor/ZYMOGENETICS) of 7.7.2006
The rationale for a type 17 signature in the pathogenesis of spondyloarthritis SpA has been increasing and being ratified in studies recently. IL-7 is a cytokine whose ability to stimulate IL production in both innate and adaptive immunity cells has made it a promising target not only for a better understanding of the disease as well as an important potential therapeutic target in patients with SpA. The human interleukin-7 gene IL-7 is located on chromosome 8q, and its molecular weight is
Cytokines are non-immunoglobulin proteins and glycoproteins produced by a wide variety of cells, in response to any immune stimulus. Cytokines are signaling molecules that send downstream signals to various cells through a number of signal transduction pathways and act further by binding to specific membrane receptors cytokine receptors on the cell surface.
Родители согласились. Хотя Энсей Танкадо никогда прежде не видел компьютера, он как будто инстинктивно знал, как с ним обращаться. Компьютер открыл перед ним мир, о существовании которого он даже не подозревал, и вскоре заполнил всю его жизнь.
Убедить абсолютно незнакомого человека отдать вам золотое кольцо скорее всего будет весьма непросто, поэтому Беккер хотел заручиться хотя бы одним преимуществом.
Но зачем он вам об этом сообщил? - спросила Сьюзан. - Хотел предложить вам купить этот алгоритм. - Нет.